Beclin 2 Functions in Autophagy, Degradation of G Protein-Coupled Receptors, and Metabolism

: He CC, Wei YJ, Sun K, Li BH, Dong XN, Zou ZJ, Liu Y, Kinch LN, Khan S, Sinha S, Xavier RJ, Grishin NV, Xiao GH, Eskelinen EL, Scherer PE, Whistler JL, Levine B, Levine B

Publisher: CELL PRESS

: 2013

: Cell

: CELL

: 154

: 5

: 1085

: 1099

: 15

: 0092-8674

DOI: https://doi.org/10.1016/j.cell.2013.07.035

The molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways remain incompletely understood. Here, we identified a previously uncharacterized mammalian-specific protein, Beclin 2, which, like Beclin 1, functions in autophagy and interacts with class III PI3K complex components and Bcl-2. However, Beclin 2, but not Beclin 1, functions in an additional lysosomal degradation pathway. Beclin 2 is required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) through its interaction with GASP1. Beclin 2 homozygous knockout mice have decreased embryonic viability, and heterozygous knockout mice have defective autophagy, increased levels of brain cannabinoid 1 receptor, elevated food intake, and obesity and insulin resistance. Our findings identify Beclin 2 as a converging regulator of autophagy and GPCR turnover and highlight the functional and mechanistic diversity of Beclin family members in autophagy, endolysosomal trafficking, and metabolism.